MiR-9-5p and miR-106a-5p dysregulated in CD4+ T-cells of multiple sclerosis patients and targeted essential factors of T helper17/regulatory T-cells differentiation

Document Type: Original Article


1 Molecular Genetics Department, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

2 Division of Cellular and Molecular Biology, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran

3 Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran

4 Institute for Nanoscience and Nanotechnology, Sharif University of Technology, Tehran, Iran


Objective(s): Multiple sclerosis (MS) is considered as a chronic type of an inflammatory disease characterized by loss of myelin of CNS.Recent evidence indicates that Interleukin 17 (IL-17)-producing T helper cells (Th17 cells) population are increased and regulatory T cells (Treg cells) are decreased in MS. Despite extensive research in understanding the mechanism of Th17 and Treg differentiation, the role of microRNAs in MS is not completely understood. Thereby, as a step closer, we analyzed the expression profile of miR-9-5p and miR-106a-5p, and protein level of retinoic acid receptor (RAR)-related orphan receptor C (RORC; Th17 master transcription factor) as direct target of miR-106a-5p and forkhead box P3 (FOXP3; Treg master transcription factor) as indirect target of miR-9-5p in CD4+ T cells in two groups of relapsing and remitting in our relapsing-remitting MS (RR-MS) patients.
Materials and Methods:Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was utilized to assess the expression of miRNAs and mRNAs, in 40 RR-MS patients and 11 healthy individuals. Thus, FOXP3 and RAR-related orphan receptor γt (RORγt) was assessed in CD4+T-cells by flow cytometry. We also investigated the role of these miRNAs in Th17/Treg differentiation pathway through bioinformatics tools.
Results: An up-regulation of miR-9-5p and down-regulation of miR-106a-5p in relapsing phase of MS patients were observed compared to healthy controls. RORC and FOXP3 wereup-regulated in relapsing and remitting phases of MS, respectively.
Conclusion: Expression pattern of miR-9-5p and miR-106a-5p and their targets suggest a possible inducing role of miR-9-5p and suppressing role of miR-106a-5p in differentiation pathway of Th17 cells during MS pathogenesis.


Main Subjects

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